Elucidating solvent effects on lipase-catalyzed peroxyacid synthesis through activity-based kinetics and molecular dynamics.

Peroxyacid synthesis is the first step in Prilezhaev epoxidation, which is an industrial method to form epoxides. Motivated by the development of a kinetic model as a tool for solvent selection, the effect of solvent type and acid chain length on the lipase-catalyzed peroxyacid synthesis was studied. A thermodynamic activity-based ping-pong kinetic expression was successfully applied to predict the effect of the reagent loadings in hexane. The activity-based reaction quotients provided a prediction of solvent-independent equilibrium constants. However, this strategy did not achieve satisfactory estimations of initial rates in solvents of higher polarity. The lack of compliance with some assumptions of this methodology could be confirmed through molecular dynamics calculations i.e. independent solvation energies and lack of solvent interaction with the active site. A novel approach is proposed combining the activity-based kinetic expression and the free binding energy of the solvent with the active site to predict kinetics upon solvent change. Di-isopropyl ether generated a strong interaction with the enzyme's active site, which was detrimental to kinetics. On the other hand, toluene or limonene gave moderate interaction with the active site rendering improved catalytic yield compared with less polar solvents, a finding sharpened when peroctanoic acid was produced.

Low rCBV values in glioblastoma tumor progression under chemoradiotherapy.

PURPOSE: After standard treatment for glioblastoma, perfusion MRI remains challenging for differentiating tumor progression from post-treatment changes. Our objectives were (1) to correlate rCBV values at diagnosis and at first tumor progression and (2) to analyze the relationship of rCBV values at tumor recurrence with enhancing volume, localization of tumor progression, and time elapsed since the end of radiotherapy in tumor recurrence. METHODS: Inclusion criteria were (1) age > 18 years, (2) histologically confirmed glioblastoma treated with STUPP regimen, and (3) tumor progression according to RANO criteria > 12 weeks after radiotherapy. Co-registration of segmented enhancing tumor VOIs with dynamic susceptibility contrast perfusion MRI was performed using Olea Sphere software. For tumor recurrence, we correlated rCBV values with enhancing tumor volume, with recurrence localization, and with time elapsed from the end of radiotherapy to progression. Analyses were performed with SPSS software. RESULTS: Sixty-four patients with glioblastoma were included in the study. Changes in rCBV values between diagnosis and first tumor progression were significant (p < 0.001), with a mean and median decreases of 32% and 46%, respectively. Mean rCBV values were also different (p < 0.01) when tumors progressed distally (radiation field rCBV values of 1.679 versus 3.409 distally). However, changes and, therefore, low rCBV values after radiotherapy in tumor recurrence were independent of time. CONCLUSION: Chemoradiation alters tumor perfusion and rCBV values may be decreased in the setting of tumor progression. Changes in rCBV values with respect to diagnosis, with low rCBV in tumor progression, are independent of time but related to the site of recurrence.

Clinical standards for the diagnosis and management of asthma in low- and middle-income countries.

BACKGROUND: The aim of these clinical standards is to aid the diagnosis and management of asthma in low-resource settings in low- and middle-income countries (LMICs).METHODS: A panel of 52 experts in the field of asthma in LMICs participated in a two-stage Delphi process to establish and reach a consensus on the clinical standards.RESULTS: Eighteen clinical standards were defined: Standard 1, Every individual with symptoms and signs compatible with asthma should undergo a clinical assessment; Standard 2, In individuals (>6 years) with a clinical assessment supportive of a diagnosis of asthma, a hand-held spirometry measurement should be used to confirm variable expiratory airflow limitation by demonstrating an acute response to a bronchodilator; Standard 3, Pre- and post-bronchodilator spirometry should be performed in individuals (>6 years) to support diagnosis before treatment is commenced if there is diagnostic uncertainty; Standard 4, Individuals with an acute exacerbation of asthma and clinical signs of hypoxaemia or increased work of breathing should be given supplementary oxygen to maintain saturation at 94-98%; Standard 5, Inhaled short-acting beta-2 agonists (SABAs) should be used as an emergency reliever in individuals with asthma via an appropriate spacer device for metered-dose inhalers; Standard 6, Short-course oral corticosteroids should be administered in appropriate doses to individuals having moderate to severe acute asthma exacerbations (minimum 3-5 days); Standard 7, Individuals having a severe asthma exacerbation should receive emergency care, including oxygen therapy, systemic corticosteroids, inhaled bronchodilators (e.g., salbutamol with or without ipratropium bromide) and a single dose of intravenous magnesium sulphate should be considered; Standard 8, All individuals with asthma should receive education about asthma and a personalised action plan; Standard 9, Inhaled medications (excluding dry-powder devices) should be administered via an appropriate spacer device in both adults and children. Children aged 0-3 years will require the spacer to be coupled to a face mask; Standard 10, Children aged <5 years with asthma should receive a SABA as-needed at step 1 and an inhaled corticosteroid (ICS) to cover periods of wheezing due to respiratory viral infections, and SABA as-needed and daily ICS from step 2 upwards; Standard 11, Children aged 6-11 years with asthma should receive an ICS taken whenever an inhaled SABA is used; Standard 12, All adolescents aged 12-18 years and adults with asthma should receive a combination inhaler (ICS and rapid onset of action long-acting beta-agonist [LABA] such as budesonide-formoterol), where available, to be used either as-needed (for mild asthma) or as both maintenance and reliever therapy, for moderate to severe asthma; Standard 13, Inhaled SABA alone for the management of patients aged >12 years is not recommended as it is associated with increased risk of morbidity and mortality. It should only be used where there is no access to ICS.The following standards (14-18) are for settings where there is no access to inhaled medicines. Standard 14, Patients without access to corticosteroids should be provided with a single short course of emergency oral prednisolone; Standard 15, Oral SABA for symptomatic relief should be used only if no inhaled SABA is available. Adjust to the individual's lowest beneficial dose to minimise adverse effects; Standard 16, Oral leukotriene receptor antagonists (LTRA) can be used as a preventive medication and is preferable to the use of long-term oral systemic corticosteroids; Standard 17, In exceptional circumstances, when there is a high risk of mortality from exacerbations, low-dose oral prednisolone daily or on alternate days may be considered on a case-by-case basis; Standard 18. Oral theophylline should be restricted for use in situations where it is the only bronchodilator treatment option available.CONCLUSION: These first consensus-based clinical standards for asthma management in LMICs are intended to help clinicians provide the most effective care for people in resource-limited settings.

Cerebral amyloid angiopathy-related inflammation: clinical features and treatment response in a case series.

INTRODUCTION: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is an entity characterised by an inflammatory response to ß-amyloid deposition in the walls of cerebral microvessels. METHODS: We conducted a retrospective review of a series of patients with a diagnosis of CAA-ri according to histopathological study findings or clinical-radiological diagnostic criteria. RESULTS: The study included 7 patients (5 men) with a mean age of 79 years. Disease onset was acute or subacute in 6 patients. The most frequent symptoms were cognitive impairment (n = 6), behavioural alterations (n = 5), epileptic seizures (n = 5), focal neurological signs (n = 4), and headache (n = 2). Cerebrospinal fluid was abnormal in 3 patients (lymphocytic pleocytosis and high protein levels). The most frequent MRI findings were microbleeds (n = 7), subcortical white matter hyperintensities on T2-FLAIR sequences (n = 7), and leptomeningeal enhancement (n = 6). Lesions were bilateral in 3 patients and most frequently involved the parieto-occipital region (n = 5). Amyloid PET studies were performed in 2 patients, one of whom showed pathological findings. Two patients underwent brain biopsy, which confirmed diagnosis. All patients received immunosuppressive therapy. An initially favourable clinical-radiological response was observed in all cases, with 2 patients presenting radiological recurrence after treatment withdrawal, with a subsequent improvement after treatment was resumed. CONCLUSIONS: Early diagnosis of CAA-ri is essential: early treatment has been shown to improve prognosis and reduce the risk of recurrence. Although a histopathological study is needed to confirm diagnosis, clinical-radiological criteria enable diagnosis without biopsy.

Quantum-resistance in blockchain networks.

The advent of quantum computing threatens blockchain protocols and networks because they utilize non-quantum resistant cryptographic algorithms. When quantum computers become robust enough to run Shor's algorithm on a large scale, the most used asymmetric algorithms, utilized for digital signatures and message encryption, such as RSA, (EC)DSA, and (EC)DH, will be no longer secure. Quantum computers will be able to break them within a short period of time. Similarly, Grover's algorithm concedes a quadratic advantage for mining blocks in certain consensus protocols such as proof of work. Today, there are hundreds of billions of dollars denominated in cryptocurrencies and other digital assets that rely on blockchain ledgers as well as thousands of blockchain-based applications storing value in blockchain networks. Cryptocurrencies and blockchain-based applications require solutions that guarantee quantum resistance in order to preserve the integrity of data and assets in these public and immutable ledgers. The quantum threat and some potential solutions are well understood and presented in the literature. However, most proposals are theoretical, require large QKD networks, or propose new quantum-resistant blockchain networks to be built from scratch. Our work, which is presented in this paper, is pioneer in proposing an end-to-end framework for post-quantum blockchain networks that can be applied to existing blockchain to achieve quantum-resistance. We have developed an open-source implementation in an Ethereum-based (i.e., EVM compatible) network that can be extended to other existing blockchains. For the implementation we have (i) used quantum entropy to generate post-quantum key pairs, (ii) established post-quantum TLS connections and X.509 certificates to secure the exchange of information between blockchain nodes over the internet without needing a large QKD network, (iii) introduced a post-quantum second signature in transactions using Falcon-512 post-quantum keys, and (iv) developed the first on-chain verification of post-quantum signatures using three different mechanisms that are compared and analyzed: Solidity smart-contracts run by the validators for each transaction, modified EVM Opcode, and precompiled smart contracts.

Oxygen Scavenger and Antioxidant LDPE/EVOH/PET-Based Films Containing ß-Carotene Intended for Fried Peanuts (Arachis hypogaea L.) Packaging: Pilot Scale Processing and Validation Studies.

The aim of this study was to develop an oxygen scavenger and antioxidant active packaging material for fried peanuts. The packaging solution, which has been made at the laboratory previously, has been developed by cast film extrusion and is composed of low-density polyethylene-ethylene vinyl alcohol-polyethylene terephthalate (LDPE/EVOH/PET)-based films containing ß-carotene (CAR). In comparison with film without additive, developed film presented an orange colouring (higher L* and b* values and lower a* values) and an increase in oxygen induction time (OIt) from 4.5 to 14.1 min. The incorporation of ß-carotene to the formulation also brings about a significant effect on the thermal stability as maximum degradation temperatures increased around 1%. Regarding the oxygen absorption capacity of the films, values of 1.39 ± 0.10 mL O2 per g of film at laboratory scale and 1.7 ± 0.3 mL O2 per g of multilayer (ML)/LDPE_CAR were obtained, respectively, after 3 days, proving the suitability of the packaging solutions as oxygen absorbers. To validate the packaging solution, the oxidative stability of fried peanuts packed in fabricated multilayer ß-carotene bags was evaluated for 3 months at 40 °C. The hexanal content remained constant during this period. Meanwhile, peanuts packed in ML without ß-carotene increased their hexanal content to 294%. This fact indicated a lower extent of oxidation in fried peanuts compared to food samples packaged in control films, suggesting the potential of ML/LDPE_CAR films as sustainable and antioxidant food packaging systems to offer protection against lipid oxidation in foods. Sensory evaluation confirmed that ML/LDPE_CAR films provided the peanut samples with an extra aroma due to the volatile degradation products of ß-carotene (such as ß-cyclocitral or 6-methyl-5-hepten-2-ol).

Calotropin and corotoxigenin 3-O-glucopyranoside from the desert milkweed Asclepias subulata inhibit the Na+/K+-ATPase activity.

Na+/K+-ATPase is an essential transmembrane enzyme found in all mammalian cells with critical functions for cell ion homeostasis. The inhibition of this enzyme by several cardiotonic steroids (CTS) has been associated with the cytotoxic effect on cancer cell lines of phytochemicals such as ouabain and digitoxin. This study evaluated the inhibitory capacity of cardenolides calotropin and corotoxigenin 3-O-glucopyranoside (C3OG) from Asclepias subulata over the Na+/K+-ATPase activity in vitro and silico. The inhibitory assays showed that calotropin and C3OG decreased the Na+/K+-ATPase activity with IC50 values of 0.27 and 0.87 µM, respectively. Furthermore, the molecules presented an uncompetitive inhibition on Na+/K+-ATPase activity, with Ki values of 0.2 µM to calotropin and 0.5 µM to C3OG. Furthermore, the molecular modeling indicated that calotropin and C3OG might interact with the Thr797 and Gln111 residues, considered essential to the interaction with the Na+/K+-ATPase. Besides, these cardenolides can interact with amino acid residues such as Phe783, Leu125, and Ala323, to establish hydrophobic interactions on the binding site. Considering the results, these provide novel evidence about the mechanism of action of cardenolides from A. subulata, proposing that C3OG is a novel cardenolide that deserves further consideration for in vitro cellular antiproliferative assays and in vivo studies as an anticancer molecule.

Advanced catalytic oxidation coupled to biological systems to treat pesticide-contaminated water: A review on technological trends and future challenges.

This article had the one and only objective of consolidating the couplings of advanced oxidation processes and biological systems in the decontamination of wastewater with pesticide content reported in the Scopus and Web of Science databases, through a critical analysis of which have been the most used, what methodologies have been implemented to develop them, identifying the objectives of each work, determining the success of the research and where the main niches of knowledge are, which can lead to the generation of new scientific knowledge as well as future trends. A co-occurrence analysis was carried out through the VOSViewer software to determine the most associated key words with the treatment configurations described above. Fenton and Photo-Fenton processes, heterogeneous photocatalysis TiO2/UV, electrocatalysis, ozonization and a particular case of hydrodynamic cavitation-ozone as main advanced oxidation processes, together with advanced biological processes such as sequential batch bioreactor (SBR), membrane bioreactor (MBR), mobile bed biofilm reactor (MBBR); biodegradability and toxicity tests with bacterial strains and surface wetlands, whose treatment philosophy is activated sludge. The main future trends are the reuse of treated wastewater, the analysis and control of costs towards the efficient use of resources and the primary study of the byproducts generated in advanced oxidation to improve the efficiencies in the coupling.

Prediction of Variable-Length B-Cell Epitopes for Antipeptide Paratopes Using the Program HAPTIC.

BACKGROUND: B-cell epitope prediction for antipeptide antibody responses enables peptide-based vaccine design and related translational applications. This entails estimating epitopeparatope binding free-energy changes from antigen sequence; but attempts to do so assuming uniform epitope length (e.g., of hexapeptide sequences, each spanning a typical paratope diameter when fully extended) have neglected empirically established variation in epitope length. OBJECTIVE: This work aimed to develop a sequence-based physicochemical approach to variablelength B-cell epitope prediction for antipeptide paratopes recognizing flexibly disordered targets. METHODS: Said approach was developed by analogy between epitope-paratope binding and protein folding modeled as polymer collapse, treating paratope structure implicitly. Epitope-paratope binding was thus conceptually resolved into processes of epitope compaction, collapse and contact, with epitope collapse presenting the main entropic barrier limiting epitope length among nonpolyproline sequences. The resulting algorithm was implemented as a computer program, namely the Heuristic Affinity Prediction Tool for Immune Complexes (HAPTIC), which is freely accessible via an online interface (http://badong.freeshell.org/haptic.htm). This was used in conjunction with published data on representative known peptide immunogens. RESULTS: HAPTIC predicted immunodominant epitope sequences with lengths limited by penalties for both compaction and collapse, consistent with known paratope-bound structures of flexibly disordered epitopes. In most cases, the predicted association constant was greater than its experimentally determined counterpart but below the predicted upper bound for affinity maturation in vivo. CONCLUSION: HAPTIC provides a physicochemically plausible means for estimating the affinity of antipeptide paratopes for sterically accessible and flexibly disordered peptidic antigen sequences by explicitly considering candidate B-cell epitopes of variable length.

Prospective Study in Children with Complicated Urinary Tract Infection Treated with Autologous Bacterial Lysates.

Antimicrobial bacteria resistance is an important problem in children with recurrent urinary tract infections (rUTI), thus it is crucial to search for alternative therapies. Autologous bacterial lysates (ABL) may be a potential treatment for rUTI. Twenty-seven children with rUTI were evaluated for one year, urine and stool cultures were performed, 10 colonies of each culture were selected and those identified as Escherichia coli were characterized by serology. For patients who presented ≥105 UFC/mL, an ABL was manufactured and administered orally (1 mL/day) for a month. Twelve children were monitored for ≥1-year, 218 urine and 11 stool samples were analyzed. E. coli (80.5%) was the main bacteria isolated from urine and feces (72%). E. coli of classical urinary serotypes (UPEC), O25:H4, O75:HNM, and O9:HNM were identified in patients with persistent urinary infection (pUTI). In 54% of patients treated with ABL, the absence of bacteria was observed in urine samples after 3 months of treatment, 42% of these remained without UTI between 10-12 months. It was observed that the use of ABL controlled the infection for almost 1 year in more than 60% of the children. We consider it necessary to develop a polyvalent immunogen for the treatment and control of rUTI.

Volatile Profile of Nuts, Key Odorants and Analytical Methods for Quantification.

The presence of nuts in diets has notably increased due to their composition, and the presence of antioxidants and their unsaturated fatty acid profile has led to a considerable increase in their consumption. The volatile profile of nuts is important from different points of view. It affects consumer's selection, influences raw material selection for the production of composite foods, dictates variety selection in breeding programs, and, from a quality perspective, its changes can indicate food degradation or alteration. A review of the published bibliography concerning the determination of volatiles in nuts has been carried out. The information retrieved has been divided into four main sections. First, a discussion on the main volatiles present in nuts is performed; next, a revision of the methods used to determine the volatiles is presented; and, finally, two sections describing how harvesting conditions, healthy state and the thermal treatment of nuts modifies their volatile profile are added. Analysis of the published bibliography denoted the complexity of volatile determination and the different variables that can modify the compounds present in the volatile fraction of nuts.

Quantum tunneling and quantum walks as algorithmic resources to solve hard K-SAT instances.

We present a new quantum heuristic algorithm aimed at finding satisfying assignments for hard K-SAT instances using a continuous time quantum walk that explicitly exploits the properties of quantum tunneling. Our algorithm uses a Hamiltonian [Formula: see text] which is specifically constructed to solve a K-SAT instance F. The heuristic algorithm aims at iteratively reducing the Hamming distance between an evolving state [Formula: see text] and a state that represents a satisfying assignment for F. Each iteration consists on the evolution of [Formula: see text] (where j is the iteration number) under [Formula: see text], a measurement that collapses the superposition, a check to see if the post-measurement state satisfies F and in the case it does not, an update to [Formula: see text] for the next iteration. Operator [Formula: see text] describes a continuous time quantum walk over a hypercube graph with potential barriers that makes an evolving state to scatter and mostly follow the shortest tunneling paths with the smaller potentials that lead to a state [Formula: see text] that represents a satisfying assignment for F. The potential barriers in the Hamiltonian [Formula: see text] are constructed through a process that does not require any previous knowledge on the satisfying assignments for the instance F. Due to the topology of [Formula: see text] each iteration is expected to reduce the Hamming distance between each post measurement state and a state [Formula: see text]. If the state [Formula: see text] is not measured after n iterations (the number n of logical variables in the instance F being solved), the algorithm is restarted. Periodic measurements and quantum tunneling also give the possibility of getting out of local minima. Our numerical simulations show a success rate of 0.66 on measuring [Formula: see text] on the first run of the algorithm (i.e., without restarting after n iterations) on thousands of 3-SAT instances of 4, 6, and 10 variables with unique satisfying assignments.

Double-Function Oxygen Scavenger and Aromatic Food Packaging Films Based on LDPE/Polybutadiene and Peanut Aroma.

The aim of this study was to develop a double function active packaging material for nuts. The packaging solution, on the one hand, integrated polybutadiene (PB) as an oxygen scavenger and, on the other hand, it incorporated peanut aroma (PA) to improve customer's sensorial experience. Different formulations based on low density polyethylene (LDPE), commercial PA (5 wt %) and PB at two levels (5 wt % and 13 wt %) were obtained by cast film extrusion. The obtained films were compared in terms of their mechanical, structural, optical and thermal properties confirming a plasticizing effect of PA and PB resulting in an increase in the ductility of the polymer and in a slight decrease in the thermal properties, maintaining their transparency. Regarding the oxygen capacity of the films, values of 4.4 mL and 2.7 mL O2 g-1 film were obtained for PE/PA/PB13 and PE/PA/PB5, respectively, after 6 days proving the suitability of the UV irradiation treatment in improving the oxygen absorption capacity of PB without the need of a metal catalyst. The aroma retention capacity into the polymer matrix was also evaluated in the developed formulations. The incorporation of PB in 13 wt % into a LDPE matrix improved the PA retention. This behavior was attributed to the ability of PB in enhancing cross-linking of LDPE as the concentration of PB increases. The results suggested the potential of PE/PB/PB13 films as oxygen scavenger and aromatic food packaging system to offer protection against lipid oxidation in nuts.

Brain and Lung Imaging Correlation in Patients with COVID-19: Could the Severity of Lung Disease Reflect the Prevalence of Acute Abnormalities on Neuroimaging? A Global Multicenter Observational Study.

PURPOSE: Our aim was to study the association between abnormal findings on chest and brain imaging in patients with coronavirus disease 2019 (COVID-19) and neurologic symptoms. MATERIALS AND METHODS: In this retrospective, international multicenter study, we reviewed the electronic medical records and imaging of hospitalized patients with COVID-19 from March 3, 2020, to June 25, 2020. Our inclusion criteria were patients diagnosed with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection with acute neurologic manifestations and available chest CT and brain imaging. The 5 lobes of the lungs were individually scored on a scale of 0-5 (0 corresponded to no involvement and 5 corresponded to >75% involvement). A CT lung severity score was determined as the sum of lung involvement, ranging from 0 (no involvement) to 25 (maximum involvement). RESULTS: A total of 135 patients met the inclusion criteria with 132 brain CT, 36 brain MR imaging, 7 MRA of the head and neck, and 135 chest CT studies. Compared with 86 (64%) patients without acute abnormal findings on neuroimaging, 49 (36%) patients with these findings had a significantly higher mean CT lung severity score (9.9 versus 5.8, P < .001). These patients were more likely to present with ischemic stroke (40 [82%] versus 11 [13%], P < .0001) and were more likely to have either ground-glass opacities or consolidation (46 [94%] versus 73 [84%], P = .01) in the lungs. A threshold of the CT lung severity score of >8 was found to be 74% sensitive and 65% specific for acute abnormal findings on neuroimaging. The neuroimaging hallmarks of these patients were acute ischemic infarct (28%), intracranial hemorrhage (10%) including microhemorrhages (19%), and leukoencephalopathy with and/or without restricted diffusion (11%). The predominant CT chest findings were peripheral ground-glass opacities with or without consolidation. CONCLUSIONS: The CT lung disease severity score may be predictive of acute abnormalities on neuroimaging in patients with COVID-19 with neurologic manifestations. This can be used as a predictive tool in patient management to improve clinical outcome.

Cerebral amyloid angiopathy-related inflammation: clinical features and treatment response in a case series. / Inflamación relacionada con angiopatía amiloide: características clínicas y respuesta al tratamiento en una serie de casos.

INTRODUCTION: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is an entity characterised by an inflammatory response to ß-amyloid deposition in the walls of cerebral microvessels. METHODS: We conducted a retrospective review of a series of patients with a diagnosis of CAA-ri according to histopathological study findings or clinical-radiological diagnostic criteria. RESULTS: The study included 7 patients (5 men) with a mean age of 79 years. Disease onset was acute or subacute in 6 patients. The most frequent symptoms were cognitive impairment (n = 6), behavioural alterations (n = 5), epileptic seizures (n = 5), focal neurological signs (n = 4), and headache (n = 2). Cerebrospinal fluid was abnormal in 3 patients (lymphocytic pleocytosis and high protein levels). The most frequent MRI findings were microbleeds (n = 7), subcortical white matter hyperintensities on T2-FLAIR sequences (n = 7), and leptomeningeal enhancement (n = 6). Lesions were bilateral in 3 patients and most frequently involved the parieto-occipital region (n = 5). Amyloid PET studies were performed in 2 patients, one of whom showed pathological findings. Two patients underwent brain biopsy, which confirmed diagnosis. All patients received immunosuppressive therapy. An initially favourable clinical-radiological response was observed in all cases, with 2 patients presenting radiological recurrence after treatment withdrawal, with a subsequent improvement after treatment was resumed. CONCLUSIONS: Early diagnosis of CAA-ri is essential: early treatment has been shown to improve prognosis and reduce the risk of recurrence. Although a histopathological study is needed to confirm diagnosis, clinical-radiological criteria enable diagnosis without biopsy.

Cadmium, Lead, Copper, Zinc, and Iron Concentration Patterns in Three Marine Fish Species from Two Different Mining Sites inside the Gulf of California, Mexico.

In the Gulf of California; mineral deposits have contributed to high metal contents in coastal environments. This study examined cadmium; lead; copper; zinc; and iron contents in three fish species; Kyphosus vaigiensis (herbivore), Stegastes rectifraenum (omnivore), and Balistes polylepis (carnivore) at two mining sites. Metal concentrations were analyzed by atomic absorption spectrophotometry and stable nitrogen and carbon isotopes were estimated using mass spectrophotometry. Also, we assessed the risk to human health from the consumption of these three species based on permissible limits; although only two of them (Kyphosus and Balistes) are consumed as food. Metal concentrations differed among fish species; except for iron. The highest concentrations of metals were not always recorded in the species at the highest trophic level; i.e., Balistes. The highest concentrations (dry weight) recorded were cadmium (0.21 ± 0.03 µg g-1) and lead (1.67 ± 0.26 µg g-1), in S. rectifraenum; copper (1.60 ± 0.49 µg g-1) and zinc (67.30 ± 8.79 µg g-1), in B. polylepis; and iron (27.06 ± 2.58 µg g-1), in K. vaigiensis. Our findings show that each element accumulates differently in particular marine organisms; depending on the physiology of the species and the biogeochemistry of its habitat; which in turn is affected by the anthropogenic activities in adjacent areas. No risk of heavy metals toxicity is expected from the human consumption of the species and sites studied.

Variability of Chemical Profile in Almonds (Prunus dulcis) of Different Cultivars and Origins.

Almonds show a great variability in their chemical composition. This variability is a result of the existence of a diverse range of almond cultivars, the self-incompatibility of most almond cultivars, and the heterogeneous harvesting conditions found around the different locations where almons are grown. In the last years, the discrimination among almond cultivars has been the focal point of some research studies to avoid fraud in protected geographical indications in almond products and also for selecting the best cultivars for a specific food application or the most interesting ones from a nutritional point of view. In this work, a revision of the recent research works related to the chemical characterization and classification of almond cultivars from different geographical origins has been carried out. The content of macronutrients, tocopherols, phytosterols, polyphenols, minerals, amino acids, and volatile compounds together with DNA fingerprint have been reported as possible cultivar and origin markers. The analysis of the results showed that no individual almond compound could be considered a universal biomarker to find differences among different almond cultivars. Hence, an adequate selection of variables or the employment of metabolomics and the application of multivariate statistical techniques is necessary when classification studies are carried out to obtain valuable results. Meanwhile, DNA fingerprinting is the perfect tool for compared cultivars based on their genetic origin.

Population pharmacokinetics of cefazolin in critically ill children infected with methicillin-sensitive Staphylococcus aureus.

OBJECTIVES: Cefazolin is one of curative treatments for infections due to methicillin-sensitive Staphylococcus aureus (MSSA). Both growth and critical illness may impact the pharmacokinetic (PK) parameters. We aimed to build a population PK model for cefazolin in critically ill children in order to optimize individual dosing regimens. METHODS: We included all children (age < 18 years, body weight (BW) > 2.5 kg) receiving cefazolin for MSSA infection. Cefazolin total plasma concentrations were quantified by high-performance liquid chromatography. A data modelling process was performed with the software MONOLIX. Monte Carlo simulations were used in order to attain the PK target of 100% fT > 4 ×MIC. RESULTS: Thirty-nine patients with a median (range) age of 7 (0.1-17) years and a BW of 21 (2.8-79) kg were included. The PK was ascribed to a one-compartment model, where typical clearance and volume of distribution estimations were 1.4 L/h and 3.3 L respectively. BW, according to the allometric rules, and estimated glomerular filtration rate (eGFR) on clearance were the two influential covariates. Continuous infusion with a dosing of 100 mg/kg/day to increase to 150 mg/kg/day for children with a BW < 10 kg or eGFR >200 mL/min/1.73m2 were the best schemes to reach the PK target of 100% fT> 4 ×MIC. CONCLUSIONS: In critically ill children infected with MSSA, continuous infusion seems to be the most appropriate scheme to reach the PK target of 100 % fT > 4 ×MIC in children with normal and augmented renal function.

Single nucleotide polymorphisms on CYP2C9 gene among Filipinos and its association with post-operative pain relief via COX-2 inhibitors.

CYP2C9 gene encodes an enzyme involved in the metabolism of a wide variety of drugs which include celecoxib. This study investigated the frequencies of the alleles and genotypes of CYP2C9*1, CYP2C9*2, and CYP2C9*3 among Filipinos who underwent surgery, and to determine the association of CYP2C9 polymorphisms with post-operative pain relief via COX-2 inhibitors. Response to celecoxib was determined using the numerical rating scale (0-10) on the 24th and 48th hour of surgery. The CYP2C9 alleles were detected by real-time PCR. For CYP2C9*1 and CYP2C9*3, the allele frequencies among Filipinos were 99% and 1% respectively, which is similar with other East Asians. CYP2C9*2 alleles were not detected. The frequencies of CYP2C9*1/*1 and CYP2C9*1/*3 genotypes were 98% and 2% respectively. At 24 hours post-surgery, the average pain score was 2.57 ± 1.03, while on 48 hours post-surgery, the average pain score was 0.67 ± 0.61 among those who have the wild-type CYP2C9*1 allele. The average pain score on the 24th and 48th hour post-operatively was observed to be 2.5 ± 0.71 and 0.5 ± 0.71 respectively among two patients classified as intermediate metabolizer carrying the CYP2C9*1/*3 genotype. Low frequencies of CYP2C9 polymorphisms were observed in the present study, this pattern was similar with other Asians except Indians, and considerably lower than Caucasians. Our results suggest that CYP2C9 genotyping is not routinely needed for Filipinos but must be considered among mixed races. Consequently, a more personalized therapeutic strategy was derived from these data, resulting in good clinical outcomes and less adverse drug effects.

Quantum aspects of evolution: a contribution towards evolutionary explorations of genotype networks via quantum walks.

Quantum biology seeks to explain biological phenomena via quantum mechanisms, such as enzyme reaction rates via tunnelling and photosynthesis energy efficiency via coherent superposition of states. However, less effort has been devoted to study the role of quantum mechanisms in biological evolution. In this paper, we used transcription factor networks with two and four different phenotypes, and used classical random walks (CRW) and quantum walks (QW) to compare network search behaviour and efficiency at finding novel phenotypes between CRW and QW. In the network with two phenotypes, at temporal scales comparable to decoherence time TD, QW are as efficient as CRW at finding new phenotypes. In the case of the network with four phenotypes, the QW had a higher probability of mutating to a novel phenotype than the CRW, regardless of the number of mutational steps (i.e. 1, 2 or 3) away from the new phenotype. Before quantum decoherence, the QW probabilities become higher turning the QW effectively more efficient than CRW at finding novel phenotypes under different starting conditions. Thus, our results warrant further exploration of the QW under more realistic network scenarios (i.e. larger genotype networks) in both closed and open systems (e.g. by considering Lindblad terms).